The long-term goal of the proposed research is to characterize the regulation of renal sodium excretion. The broad objective of the current proposal is to investigate the nephron site(s) and mechanisms involved in the natriuresis following elevation of renal perfusion pressure. Our working hypothesis is that transmission of pressure to the renal interstitium activates "interstitial baroreceptors"--medullary interstitia cells. Medullary interstitial cells respond with increases in synthesis of prostaglandins leading to decreases in tubular sodium reabsorption. In addition to changes in renal perfusion pressure, a polyethylene matrix, which is chronically implanted in the renal interstitium of the rat, will be used as a tool to directly increase renal interstitial hydrostatic pressure. The in vivo relationship between hydrostatic pressure in the peritubular microcirculation, interstitium, and subsequent effects on sodium reabsorption will be studied utilizing micropuncture techniques. The in vitro relationship between hydrostatic pressure and prostaglandin production will be studied by measuring the rate of prostaglandin synthesis in medullary tissue slices subjected to different levels of pressure. The specific questions to be addressed are: 1) What is the mechanism for transmission of changes in perfusion pressure to the renal interstitium? 2) What is the link between increases in renal interstitial pressure and increase in prostaglandin synthesis? 3) What is the role of prostaglandins in the decrease of tubular sodium reabsorption following increases in renal interstitial hydrostatic pressure? 4) Is renal sympathetic tone necessary to demonstrate an effect of prostaglandin on sodium reabsorption? 5) What is the interaction of angiotensin II and prostaglandins in the pressure natriuresis phenomenon? Answers to these questions should provide an understanding of mechanisms underlying the relationship between renal perfusion pressure and sodium excretion which in turn are fundamental to the pathogenesis of arterial hypertension.